Synthetic polymer-based materials have played a vital role in modernization and thus advanced the quality of life for people everywhere (Nicholson, 2006). Humans have made extensive use of polymeric materials for at least 20,000 years, in the form of wood (polysaccharides) and animal furs, wools and silks (polypeptides); reliance on polymers cannot be expected to change soon. The scale of the need is global. Ideally, polymer production will also be renewable and sustainable. Based on current estimates, the USA can be energy-independent for perhaps 200 years. In order to be able transition at some point to alternative polymers for materials fabrication, however, alternatives must first be identified and developed in ways that make sense for manufacturing. In addition, alternatives may display novel or desirable properties that either cannot be realized, or are difficult to realize, with synthetic polymers.
The most common backbone atoms in synthetic polymers are carbon, hydrogen, and oxygen. Synthetic polymers such as plastic molded parts are currently in high demand because they are often stronger, lighter, less expensive or have a longer useful lifetime than wood or metal counterparts. Synthetic polymers, for example, are made into molded airplane parts and automobile components, disposable scientific labware, paints, glues, textiles, shoe parts, baby bottles, disposable supermarket packaging and a wide variety of other products. Nevertheless, the long-term future of synthetic materials is imperiled by fluctuations in the price of petrochemicals and the diminishing availability of precursors.
Two promising classes of alternative polymers are polysaccharides and polypeptides. Both are made naturally by living organisms. Although the roles of peptides in living organisms have been studied in great depth in the context of protein structure and function, the potential advantages of peptides for materials fabrication are still largely unknown.
A common classification scheme for proteins has three categories: membrane proteins, globular proteins and structural proteins (Voet et al., 2006). The last group is the most important one for alternative polymers for materials manufacturing. For example, some structural proteins found in spider dragline silk and mammalian connective tissue have a comparatively repetitive amino sequence and thus low sequence diversity. It is unclear, however, whether the same sequences are mostly A) products of an evolutionary optimization process for functional advantage or B) artifacts of loosely controlled gene duplication in which copies became tandem repeats in a single gene. One key hypothesis is that the amino acid composition of some structural proteins is as much a matter of gene duplication as random mutation and selection.
Previous studies of protein-based or -derived materials have produced interesting results and revealed remarkable properties. Spider silk, for example, is stronger than steel per unit mass (e.g. van Beek et al., 2002). Thousands of spider silk strands have been spun into a set of violin strings (Osaki, 2012). Current research focuses on wild-type polypeptides (endogenous or recombinant), wild-type-like polypeptides (recombinant) or structural elements based on wild-type polypeptides (recombinant or synthetic). Examples of the last category are elastin-like peptides (ELPs) and leucine zippers, which have been involved in studies on the elastic properties of biological tissues (elastin) and hydrogels for drug delivery (leucine zippers) (Urry and Parker, 2002; Petka et al., 1998). Elastin, though biodegradable, has a remarkably long half-life in vivo, where it undergoes millions of extensions and retractions over the lifetime of the organism.
Properties of elastin, resilin, wool keratins and other proteins suggest that materials made of designed polypeptides could display desirable elasticity, durability and biodegradability. It has long been assumed that the elasticity of the noted proteins is attributable to sequence, secondary structures and tertiary structures. However, certain regions of the proteins resilin and titin, for example, are known to play a crucial role in elasticity but comprise little secondary structure (Elvin et al., 2005; Hsin et al., 2011). Moreover, these regions have low amino acid sequence diversity.
The structure of every protein, including elastin and resilin, is assumed to have resulted from a long evolutionary selection process and thus to be optimized for functionality. Reverse-engineering what nature has already done, however, has two major drawbacks: First, random peptides are more similar than gene-encoded peptides to the synthetic polymers of materials manufacture, some of which have been unqualified successes. Proteins, in contrast, are essentially monodisperse, the sequences are essentially identical, and the chains tend to adopt specific secondary structures, α helices and β sheets, to fold and display specific functions (Voet et al., 2006. Second, natural helices and sheets tend to be unstable apart from the rest of the protein (Finkelstein and Ptitsyn, 2002) and random amino acid sequences are unlikely to adopt stable secondary structures or show regular patterns of persistent hydrogen bonding. Nevertheless, stable secondary structures have been designed (e.g. Regan and DeGrado, 1988), and they could enhance properties of non-biological bulk peptide materials (e.g. Petka et al., 1998). Such successes have led investigators to believe that designed materials must contain such structures, as hydrogen bonds are believed to be significant contributors to protein thermostability (Finkelstein and Ptitsyn, 2002).
At ambient temperatures, bond vibrations in most molecules, including polymers, are limited (Strobl, 2007) and double bonds do not rotate. This has significant consequences for entropy and elasticity by way of limiting the number of accessible conformations to a polymer chain. In peptide bonds, backbone rotations are further limited by electron delocalization (Voet et al., 2006). One odd feature of the peptide backbone is the presence of nitrogen in the amino group, which is a hydrogen bond donor. This feature contributes to the polar nature of the polypeptide and has significant consequences for polymer solubility in water, intra-chain structure formation, inter-chain bonding and chain entropy.
Peptides can be synthesized by ring-opening polymerization, characterized in aqueous solution by gel permeation chromatography, viscometry, circular dichroism spectroscopy and other methods and processed into 1-, 2- and 3-dimensional materials by several guided self-assembly methods: electrospinning, film casting and molding, respectively. Mechanical properties of the materials can then be determined by uniaxial tensile strength testing and other methods. However, current peptide synthesis requires prior knowledge of sequence or persistent secondary or tertiary structure.
Linear homopolypeptides and heteropolypeptides, uniform and non-uniform sequence, respectively, can be prepared by solid-phase or solution-phase methods (chemical approaches) or recombinant methods (biological approaches). These synthesis approaches have advantages and disadvantages for different purposes. For example, chemical synthesis is advantageous for small-peptide biologics production. Solution-phase approaches are usually favored for therapeutic peptides shorter than 15 amino acid residues and quantities over 100 kg, whereas complex or longer sequences are usually made by solidphase synthesis, and peptides longer than 50 residues are made by recombinant methods (Thayer, 2011). All industrial enzymes are made by biological methods.